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Article
| Open AccessPredicting vaccine effectiveness for mpox
Here, based on a systematic review and meta-analysis, the authors analyze the relationship between vaccine immunogenicity and vaccine protection against mpox and predict the durability of protection after vaccination. This helps inform the optimal vaccine deployment in a health emergency.
- Matthew T. Berry
- , Shanchita R. Khan
- & David S. Khoury
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Article
| Open AccessSARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.
- Patrick Y. A. Reinke
- , Robin Schubert
- & Thomas J. Lane
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Article
| Open AccessCharacterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria
mRNA therapeutics delivered via lipid nanoparticles are being developed for the treatment of metabolic diseases caused by protein deficiency. Here, the authors use preclinical data to develop translational PK/PD models, which scaled allometrically to humans to predict starting doses for first-in-human clinical studies for in propionic acidemia, methylmalonic acidemia, and phenylketonuria.
- Rena Baek
- , Kimberly Coughlan
- & Paolo G. V. Martini
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Article
| Open AccessSleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes
Sleep disorders increase the risk and mortality of heart disease. Here, the authors show that sleep fragmentation results in elevated copper levels in the male mouse heart and exacerbates myocardial ischemia–reperfusion injury with increased myocardial cuproptosis and apoptosis.
- Na Chen
- , Lizhe Guo
- & E. Wang
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Article
| Open AccessPersistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Standard diagnostics are often not able to fully capture submicroscopic parasite dynamics after treatment with antimalarials. In this longitudinal analysis of molecular markers of malaria parasitemia in an Ugandan cohort, authors describe persistence of markers following antimalarial therapy with dynamic and complex multiclonal infections in the initial and post-treatment periods.
- Justin Goodwin
- , Richard Kajubi
- & Sunil Parikh
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Article
| Open AccessMetabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer’s disease
Metabolic implications in AD are unclear. Here, authors found significant correlations between cognitive impairment and metabolic features in a Chinese aging cohort (n = 1397). The study highlights ammonia disturbance as a potential therapeutic target for AD.
- Tianlu Chen
- , Fengfeng Pan
- & Wei Jia
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Article
| Open AccessSeasonal antigenic prediction of influenza A H3N2 using machine learning
This study presents a machine learning model that accurately predicts seasonal antigenic changes of influenza A H3N2 using genetic data. The model’s predictions can aid influenza surveillance, vaccine strain selection, and public health management.
- Syed Awais W. Shah
- , Daniel P. Palomar
- & Matthew R. McKay
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Article
| Open AccessTargeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow
Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1.
- Tongling Huang
- , Zhaocheng Lu
- & Min Guan
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Article
| Open AccessGenetic association of inflammatory marker GlycA with lung function and respiratory diseases
Here, the authors observed significant genetic correlation of GlycA with lung function, asthma and COPD and identified ten shared loci revealing potential shared biological mechanisms involving ubiquitination and Wnt/β-catenin signaling.
- Yanjun Guo
- , Quanhong Liu
- & Weihong Chen
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Article
| Open AccessIL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube
In pelvic inflammatory disease, host immune responses to Neisseria gonorrhoeae damage Fallopian tube tissue and cause infertility. Here, Garcia et al. show that the cytokine IL-17C induces inflammatory responses, and peptidoglycan fragments reduce transcripts related to tissue integrity.
- Erin M. Garcia
- , Jonathan D. Lenz
- & Joseph P. Dillard
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Article
| Open AccessLncRNA-LncDACH1 mediated phenotypic switching of smooth muscle cells during neointimal hyperplasia in male arteriovenous fistulas
Arteriovenous fistulas are the most common vascular access points for hemodialysis, but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia. Here, the author shows that LncDACH1 regulates NIH through the HSP90/ SRPK1/ AKT signaling axis.
- Zhaozheng Li
- , Yao Zhao
- & Jundong Jiao
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Article
| Open AccessUsing genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes
Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population.
- Jie Ping
- , Guochong Jia
- & Wei Zheng
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Article
| Open AccessModelling the transmission dynamics of H9N2 avian influenza viruses in a live bird market
H9N2 avian influenza is a virus with zoonotic potential that is common in poultry in live bird markets in Asia. In this study, the authors use mathematical modelling to characterise transmission of H9N2 in live bird markets in Bangladesh and assess the effectiveness of potential interventions to reduce its circulation.
- Francesco Pinotti
- , Lisa Kohnle
- & Guillaume Fournié
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Article
| Open AccessConcomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer
Here the authors report baseline results of a population-based trial testing concomitant human papillomavirus (HPV) vaccination and HPV-based screening of young women in Sweden and, using a transmission model, suggest that this approach may reduce high-risk HPV infections.
- Laila Sara Arroyo Mühr
- , Andrea Gini
- & Joakim Dillner
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Article
| Open AccessGalectin-3 impairs calcium transients and β-cell function
Galectin-3, mainly produced and secreted by macrophages, is elevated in diabetes. Here, the authors show that galectin-3 directly interacts with voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and blocks calcium transients and subsequent insulin secretion.
- Qian Jiang
- , Qijin Zhao
- & Pingping Li
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Article
| Open AccessDopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo
Here, the authors report that schizophrenia risk variants mapping to a striatal dopamine-related gene set are associated with increased striatal dopamine synthesis capacity and increased striatal activity during reward anticipation in humans.
- Leonardo Sportelli
- , Daniel P. Eisenberg
- & Giulio Pergola
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Article
| Open AccessCost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China
Economic evaluation of utilization of digital technologies for cataract screening remains unknown. Here the authors show that digital hierarchical screening is cost-effective in China and annual screening proved to be the most cost-effective option.
- Xiaohang Wu
- , Yuxuan Wu
- & Haotian Lin
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Article
| Open AccessProtein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson’s phenotypes
The aggregation of the neuronal protein α-Synuclein is associated with the onset of Parkinson’s disease. Here the authors report a two-dimensional Fragment Assisted Structure-based technique to find antagonists of α-Synuclein aggregation and show its promise for identifying lead therapeutics for Parkinson’s disease.
- Nicholas H. Stillman
- , Johnson A. Joseph
- & Sunil Kumar
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Article
| Open AccessA secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1
Triazole antifungals are widely used and exert their action by inhibiting ergosterol biosynthesis. Here, Rybak et al show that these drugs both inhibit ergosterol biosynthesis and induce accumulation of pathway intermediates that directly induce inhibition of sterol synthesis.
- Jeffrey M. Rybak
- , Jinhong Xie
- & Jarrod R. Fortwendel
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Article
| Open AccessDynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
In this study, the authors report the case of a patient who underwent lung transplantation and subsequently developed COVID-19 that resulted in persistent infection. Following antiviral treatment, SARS-CoV-2 (BA.5) showed dynamic genetic diversity with remdesivir resistant mutations leading to enhanced fusogenicity.
- Hidetoshi Igari
- , Seiichiro Sakao
- & Eiji Ido
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Article
| Open AccessReservoir displacement by an invasive rodent reduces Lassa virus zoonotic spillover risk
Mastomys natalensis is a rodent species native to West Africa that is the primary reservoir host for Lassa virus. Here, the authors investigate whether the invasive rodent Rattus rattus decreases M. natalensis density and could therefore indirectly decrease zoonotic transmission of Lassa virus to humans.
- Evan A. Eskew
- , Brian H. Bird
- & Scott L. Nuismer
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Article
| Open AccessFine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.
- Zhishan Chen
- , Xingyi Guo
- & Wei Zheng
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Article
| Open AccessDiphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects
Rare disease DEDSSH1-associated DPH1 mutations impair eEF2 diphthamide modification that leads to eEF2 as a transcriptional coactivator for p53 to enhance expression of the cell proliferation inhibitor p21, resulting in birth defects.
- Yu Shi
- , Daochao Huang
- & Weihong Song
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Article
| Open AccessMetabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites
Diagnosing inherited retinal degeneration is challenging. This exploratory study showed that metabolomic profiles differ among different subtypes of IRD, and potential biomarkers could be identified to facilitate diagnosis workflow in the near future.
- Wei-Chieh Wang
- , Chu-Hsuan Huang
- & Ta-Ching Chen
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Article
| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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Article
| Open AccessBat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets
In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.
- Nico Joel Halwe
- , Lea Hamberger
- & Martin Beer
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Article
| Open AccessLoss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice
Knowledge of pathogenesis mechanisms and effective treatments for viral myocarditis is lacking. Here, Wang et al show that loss of TRIM29 and PERK inhibitor mitigate viral myocarditis by attenuating PERK-driven ER stress and ROS responses in male mice.
- Junying Wang
- , Wenting Lu
- & Junji Xing
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Article
| Open AccessOverlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange
Streptococcus dysgalactiae subsp. equisimilis is closely related to Streptococcus pyogenes and colonises the same sites in humans. This study examines cross-species transmission interactions and genetic exchange in a high disease burden setting.
- Ouli Xie
- , Cameron Zachreson
- & Steven Y. C. Tong
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Article
| Open AccessA giant virus infecting the amoeboflagellate Naegleria
This is the first report on a virus infecting the amoeboflagellate Naegleria, including the lethal human pathogen N. fowleri. The new virus isolate, Catovirus naegleriensis (Naegleriavirus, NiV), shows hallmarks of giant viruses (Nucleocytoviricota) and unique adaptations to its protist host.
- Patrick Arthofer
- , Florian Panhölzl
- & Matthias Horn
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Article
| Open AccessLong-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity
Detailed data on SARS-CoV-2 dynamics in Africa remain limited. Here, the authors use longitudinal serology and SARS-CoV-2 sequencing data from Ethiopia between August 2020 and July 2022 to characterise circulating variants, identify infection pathways, and explore cross-immunity properties.
- Simon Merkt
- , Solomon Ali
- & Andreas Wieser
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Article
| Open AccessEstimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
Malaria transmission is affected by temperature but this relationship is not well characterised. Here, the authors experimentally determine the effect of temperature on parasite development in the mosquito and model how it impacts malaria transmission in Kenya under current and future climate scenarios.
- Eunho Suh
- , Isaac J. Stopard
- & Matthew B. Thomas
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Article
| Open AccessMulti-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
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Article
| Open AccessAZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation
The hypothalamus is essential for energy regulation, with POMC neurons crucial for controlling food intake and energy balance. Here, the authors show that AZGP1 improves leptin sensitivity in POMC neurons, aiding in weight loss and energy use by altering leptin-JAK2-STAT3 signalling.
- Sheng Qiu
- , Qinan Wu
- & Mengliu Yang
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Article
| Open AccessBispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial
CAR-T cell therapies targeting BCMA have shown promising responses in patients with multiple myeloma (MM), however primary resistance and relapse are frequently observed. Here the authors report the results of a phase I//II study of bispecific CAR T-cells targeting BCMA and CD19 in relapsed/refractory MM.
- Ming Shi
- , Jiaojiao Wang
- & Jiang Cao
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Article
| Open AccessAn esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease.
- Jiarui Ding
- , John J. Garber
- & Ramnik J. Xavier
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Article
| Open AccessMonkeypox virus genomic accordion strategies
The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.
- Sara Monzón
- , Sarai Varona
- & Gustavo Palacios
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Article
| Open AccessEmerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Many emerging SARS-CoV-2 variants partially escape the humoral immune response. Here, Liu et al. characterize 28 antibodies from BA.4/5 breakthrough infections and find attrition of neutralization and complete loss of function for variants with Spike mutations at positions 455 and 456.
- Chang Liu
- , Raksha Das
- & Gavin R. Screaton
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Article
| Open AccessMechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2
The biogenesis of iron-sulfur proteins in eukaryotes is initiated by the mitochondrial core ISC complex. Here, the authors provide structural, biochemical and spectroscopic data to characterize sulfur transfer intermediates in the core ISC complex.
- Vinzent Schulz
- , Ralf Steinhilper
- & Roland Lill
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Article
| Open AccessUltrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
The recent monkeypox outbreak highlighted the need for rapid and accurate diagnosis of this disease. Here, authors develop an ultrasensitive and streamlined CRISPR assay using miniaturized device, which can detect monkeypox virus in rash fluid swab, oral swab, saliva, and urine within 15 minutes.
- Yunxiang Wang
- , Hong Chen
- & Shengqi Wang
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Article
| Open AccessPerinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study
The impacts of maternal SARS-CoV-2 infection on newborns are not well understood. Here, the authors perform a national cohort study using data on births in the UK from March 2020—March 2022 and find that moderate to severe maternal COVID-19 was associated with adverse perinatal outcomes.
- Hilde Marie Engjom
- , Rema Ramakrishnan
- & Marian Knight
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Article
| Open AccessPositive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution
SARS-CoV-2 constantly evolves but the roles of resulting mutations are not always clear. In this study, the authors report that ORF8 knockout confers a fitness advantage to SARS-CoV-2 using genomic surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.
- Cassia Wagner
- , Kathryn E. Kistler
- & Trevor Bedford
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Article
| Open AccessLipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis
Oxidative stress triggers lipid accumulation in cells by sequestering triglycerides in lipid droplets. Here, the authors show that lipopolysaccharide-binding protein interacts with redox sensor PRDX4 to control lipid-redox balance and promotes triglyceride accumulation in droplets by capturing unsaturated lipids.
- Qilun Zhang
- , Xuting Shen
- & Haoshu Fang
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Article
| Open AccessEpidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Coccidioidomycosis, a WHO-listed mycosis, is neglected in South America. Analysis of 292 cases in Brazil, often tied to armadillo hunting, unveils unique disease patterns, environmental factors and pathogen genetics causing the disease.
- Kelsen Dantas Eulálio
- , Daniel R. Kollath
- & Marcus de Melo Teixeira
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Article
| Open AccessSubthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control
How movement speed is neurally modulated remains poorly understood. Here, the authors recorded invasive brain signals in Parkinson’s disease patients during drawing and deep brain stimulation, showing a context-dependent relationship between reductions of movement acceleration and dynamic activity of the basal ganglia.
- Manuel Bange
- , Gabriel Gonzalez-Escamilla
- & Sergiu Groppa
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Article
| Open AccessSplice modulators target PMS1 to reduce somatic expansion of the Huntington’s disease-associated CAG repeat
Somatic expansion of a CAG repeat in HTT drives onset of Huntington’s disease. Using a human cell line model and splice modulators, here the authors show that PMS1 is an enhancer of CAG repeat expansion, making it a target for therapeutic intervention.
- Zachariah L. McLean
- , Dadi Gao
- & James F. Gusella
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Article
| Open AccessImmunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
In this study, Giron et al. find that people living with chronic HIV experience accelerated aging-associated alterations in antibody glycans. These alterations, attributed to senescence enzymes, predict comorbidities and reduce the antiviral function of antibodies.
- Leila B. Giron
- , Qin Liu
- & Mohamed Abdel-Mohsen
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Article
| Open AccessThe genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus
This study on respiratory syncytial virus (RSV) reveals global genomic gaps. Using INFORM-RSV data, it uncovers selection’s impact on RSVA and RSVB diversity. Analysing full genomes, it highlights non-neutral epidemic processes. The research emphasises air travel’s influence on global spread, underscoring the need for comprehensive RSV genomic surveillance.
- Annefleur C. Langedijk
- , Bram Vrancken
- & Shabir A. Madhi
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Article
| Open AccessDHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Inflammatory bowel disease (IBD) is featured with epithelial barrier dysfunction, however, the underlying mechanism is less clear. Here, the authors show that DHX9 deficiency in intestinal stem cells (ISCs) induces accumulation of abnormal R-loops and subsequent genomic instability, leading to impairment of ISCs and development of IBD.
- Xingxing Ren
- , Qiuyuan Liu
- & Shu Zhu
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Article
| Open AccessImmunoregulatory role of the gut microbiota in inflammatory depression
Inflammatory depression is a treatment-resistant subtype of depression. Here, the authors show that patients with inflammatory depression exhibit a disrupted microbiota, which upon FMT in mice leads to increased peripheral and central inflammatory factors, intestinal mucosal permeability, and depressive and anxiety-like behaviors. Probiotic administration ameliorates the disease phenotype.
- Penghong Liu
- , Zhifen Liu
- & Kerang Zhang
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